1. Field of the Invention
The chemical processes of the present invention provide novel antibacterial agents of the .beta.-lactam type containing a hitherto unknown nucleus and useful intermediates for the synthesis of said antibacterial agents.
2. Description of the Prior Art
Penicillins and cephalosporins comprise a group of well-known antibacterial agents commonly grouped together as a class called .beta.-lactam antibiotics. Most of the work in this field has been done, broadly speaking, with 6-aminopenicillanic acid, 7-aminocephalosporanic acid and derivatives thereof produced by fermentation or chemical transformation of the natural products. Despite the extensive progress made in preparing active derivatives of 6-aminopenicillanic acid and 7-aminocephalosporanic acid, there is a continuing search for synthetic and semisynthetic routes to new families of .beta.-lactam antibiotics which may possess more advantageous properties than those derived from the known penicillin and cephalosporin nuclei.
Literature publications relating to other more non-conventional .beta.-lactam-containing antibiotics include the following:
a. Belgian Patent No. 846,933 discloses the compound of the formula ##STR2## which has been isolated from fermentation of Streptomyces clavuligerus. This compound, named clavulinac acid, possesses a low order of antibacterial activity but inhibits the action of certain .beta.-lactamases and reportedly enhances the in vitro and in vivo activity of some penicillins and cephalosporins.
b. U.K. Patent No. 1,467,413 discloses the fermentation product having the formula ##STR3## which is reported to possess some antibacterial activity and to be a .beta.-lactamase inhibitor.
c. Brown, et al. in J.C.S. Chem. Comm., 359-360 (1977) disclose preparation of the compound of the formula ##STR4## There is no indication from the publication that the compound possesses any antibacterial activity.
d. U.S. Pat. No. 3,950,357 describes a fermentation process for producing thienamycin, the compound of the formula ##STR5##
Thienamycin is reported to be a highly potent broad-spectrum antibiotic.
e. Belgian Patent No. 849,118 (equivalent U.S. Pat. No. is 4,070,477) discloses a series of 6-amino-2-penem-3-carboxylic acid derivatives of the formula ##STR6## where R.sub.1.sup.a is hydrogen or an N-protecting group, R.sub.1.sup.b is hydrogen or acyl (or R.sub.1.sup.a and R.sub.1.sup.b taken together are a divalent N-protecting group), --CO--R.sub.2 is carboxyl or a protected carboxyl group and R.sub.3 is hydrogen or a C-bonded organic group. The compounds and their salts are said to possess antibacterial activity. No compounds are disclosed in the publication which do not contain the amino or acylamido moiety at the 6-position of the .beta.-lactam ring.